title: Weak functional coupling of the melanocortin-1 receptor expressed in human adipocytes.
abstract: The melanocortin (MC) receptor type-1 (MC1-R) is the only one of the five MC receptor subtypes expressed in human adipose tissue explants, human mesenchymal stem cells (MSCs), and MSC-derived adipocytes. Following our recent expression studies (Obesity 2007, 15, 40-49), we now investigated the functional role of MC1-R in these tissues and cells to deduce the coupling state of MC1-R to intracellular output signals in human fat cells and tissue. Expression of MC1-R by undifferentiated and differentiated MSCs was quantified by real-time TaqMan PCR. Intracellular output signals (cAMP, lipolysis, secretion of IL-6, IL-10, and TNF-alpha), as well as effects on the metabolic rate and proliferation of human MSCs were analyzed by standard assays, exposing undifferentiated and differentiated MSCs and, in part, human adipose tissue explants to the potent MC1-R agonist, [Nle(4), D-Phe(7)]-alpha-MSH (NDP-MSH). This agonist induced a weak cAMP signal in MSC-derived adipocytes. However, it did not affect lipolysis in these cells or in adipose tissue explants, nor did it modulate cytokine release and mRNA expression of IL-6, IL-8, and TNF-alpha upon LPS stimulation. In undifferentiated MSCs, NDP-MSH did not alter the metabolic rate, but it showed a significant antiproliferative effect. Therefore, it appears that MC1-R-effector coupling in (differentiated) human adipocytes is too weak to induce a regulatory effect on lipolysis or inflammation; by contrast, MC1-R stimulation in undifferentiated MSCs induces an inhibitory signal on cell proliferation.
authors.affiliation: Department of Biomedicine, University Hospital, Basel, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Hoch
authors.forename: Estelle
authors.initials: E
authors.lastname: Hirzel
authors.forename: Peter
authors.initials: P
authors.lastname: Lindinger
authors.forename: Alex N
authors.initials: AN
authors.lastname: Eberle
authors.forename: Philippe
authors.initials: P
authors.lastname: Linscheid
authors.forename: Ivan
authors.initials: I
authors.lastname: Martin
authors.forename: Thomas
authors.initials: T
authors.lastname: Peters
authors.forename: Ralph
authors.initials: R
authors.lastname: Peterli
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000345:Affinity Labels / Q000494:pharmacology; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000187:drug effects / Q000378:metabolism; D008066:Lipolysis / Q000187:drug effects; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D044102:Receptor, Melanocortin, Type 1 / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism; D055815:Young Adult; D000521:alpha-MSH / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000345:Affinity Labels; D016588:Anticarcinogenic Agents; D015850:Interleukin-6; D016209:Interleukin-8; D044102:Receptor, Melanocortin, Type 1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D000521:alpha-MSH; C027756:MSH, 4-Nle-7-Phe-alpha-